Current work in the development of smart materials and hydrogels has opened the door to a host of potential applications in such fields as drug delivery, tissue engineering and microfluidics. Hydrogels are composed of water soluble monomers which are physically or covalently cross-linked to form three dimensional polymer networks. This cross-linking can often times be controlled by the incorporation of stimulus responsive proteins or peptides into the monomeric building block. Stimuli such as pH, temperature or ionic strength can be used to induce changes which can regulate the assembly of hydrogel networks. Examples of protein domains which facilitate environmentally cued gelation include elastin-like peptides, calmodulin, and α-helical leucine zipper domains.
Helical leucine zippers are a structural motif found in DNA binding proteins. The name is derived from the periodic repeat of leucine residues. These hydrophobic amino acids protrude outward and run down a plane of the helix. This creates a hydrophobic driving force which leads to the formation of “zipped” coiled-coil bundles. These domains have been extensively characterized in the literature proving to be beneficial for creating stimulus responsive hydrogel networks as they assemble and dissociate in response to changes in temperature and pH. These domains have been appended to enzymes and other proteins to create functionalized hydrogel constructs.
There is a need for stimulus-responsive hydrogels in which cross-linking can be allosterically controlled. This invention addresses these needs.